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Record W4313389535 · doi:10.3389/fimmu.2022.1074740

CLIC-01: Manufacture and distribution of non-cryopreserved CAR-T cells for patients with CD19 positive hematologic malignancies

2022· article· en· W4313389535 on OpenAlexafffundabout
Natasha Kekre, Kevin A. Hay, John R. Webb, Ranjeeta Mallick, Miruna Balasundaram, Mhairi K. Sigrist, Anne-Marie Clément, Julie S. Nielsen, Jennifer Quizi, Eric Yung, Scott D. Brown, Lisa Dreolini, Daniel D. Waller, Julian Smazynski, Nicole S. Gierc, Bianca C. Loveless, Kayla Clark, Tyler Dyer, Richard T. Hogg, Leah McCormick, Michael C. Gignac, Shanti Bell, D. Maria Chapman, David A. Bond, Siao Yong, Rachel Fung, Heather M. Lockyer, Victoria Hodgson, Catherine J. Murphy, Ana Subramanian, Evelyn Wiebe, Piriya Yoganathan, Liana Medynski, Dominique C. Vaillan, Alice Black, Sheryl McDiarmid, Michael Kennah, Linda Hamelin, Kevin Song, Sujaatha Narayanan, Judith Anula Rodrigo, Stefany Dupont, Terry Hawrysh, Justin Presseau, Kednapa Thavorn, Manoj M. Lalu, Dean Fergusson, John C. Bell, Harold Atkins, Brad H. Nelson, Robert A. Holt

Bibliographic record

VenueFrontiers in Immunology · 2022
Typearticle
Languageen
FieldMedicine
TopicCAR-T cell therapy research
Canadian institutionsUniversity of VictoriaCanada's Michael Smith Genome Sciences CentreUniversity of OttawaTerry Fox Research InstituteVancouver General HospitalUniversity of British ColumbiaSimon Fraser UniversityOttawa Hospital
FundersOttawa Hospital FoundationBC Cancer Foundation
KeywordsMedicineFludarabineCytokine release syndromeCD34CyclophosphamideCD19Internal medicineLymphomaGastroenterologyOncologyImmunologyCancerAntigenChimeric antigen receptorStem cellImmunotherapyChemotherapyBiology

Abstract

fetched live from OpenAlex

Access to commercial CD19 CAR-T cells remains limited even in wealthy countries like Canada due to clinical, logistical, and financial barriers related to centrally manufactured products. We created a non-commercial academic platform for end-to-end manufacturing of CAR-T cells within Canada’s publicly funded healthcare system. We report initial results from a single-arm, open-label study to determine the safety and efficacy of in-house manufactured CD19 CAR-T cells (entitled CLIC-1901) in participants with relapsed/refractory CD19 positive hematologic malignancies. Using a GMP compliant semi-automated, closed process on the Miltenyi Prodigy, T cells were transduced with lentiviral vector bearing a 4-1BB anti-CD19 CAR transgene and expanded. Participants underwent lymphodepletion with fludarabine and cyclophosphamide, followed by infusion of non-cryopreserved CAR-T cells. Thirty participants with non-Hodgkin’s lymphoma (n=25) or acute lymphoblastic leukemia (n=5) were infused with CLIC-1901: 21 males (70%), median age 66 (range 18-75). Time from enrollment to CLIC-1901 infusion was a median of 20 days (range 15-48). The median CLIC-1901 dose infused was 2.3 × 10 6 CAR-T cells/kg (range 0.13-3.6 × 10 6 /kg). Toxicity included ≥ grade 3 cytokine release syndrome (n=2) and neurotoxicity (n=1). Median follow-up was 6.5 months. Overall response rate at day 28 was 76.7%. Median progression-free and overall survival was 6 months (95%CI 3-not estimable) and 11 months (95% 6.6-not estimable), respectively. This is the first trial of in-house manufactured CAR-T cells in Canada and demonstrates that administering fresh CLIC-1901 product is fast, safe, and efficacious. Our experience may provide helpful guidance for other jurisdictions seeking to create feasible and sustainable CAR-T cell programs in research-oriented yet resource-constrained settings. Clinical trial registration https://clinicaltrials.gov/ct2/show/NCT03765177 , identifier NCT03765177.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.057
Threshold uncertainty score0.525

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.007
GPT teacher head0.238
Teacher spread0.231 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations30
Published2022
Admission routes3
Has abstractyes

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